Selectively targeting BCL6 using a small molecule inhibitor is a potential therapeutic strategy for ovarian cancer
Min Wu, Jiuqing Xie, Yajing Xing, Lin Zhang, Huang Chen, Bin Tang, Miaoran Zhou, Shiyi Lv, Dongxia Huang, Shuyi Jian, Cili Zhou, Mingyao Liu, Weikai Guo, Yihua Chen, Zhengfang Yi
Abstract
. meanwhile, WK369 can prolong the survival of ovarian cancer-bearing mice. It is worth noting that WK369 also has significant anti-tumor effects on cisplatin-resistant ovarian cancer cell lines. Mechanistic studies have shown that WK369 can directly bind to the BCL6-BTB domain and block the interaction between BCL6 and SMRT, leading to the reactivation of p53, ATR and CDKN1A. BCL6-AKT, BCL6-MEK/ERK crosstalk is suppressed. As a first attempt, our study demonstrates that targeting BCL6 may be an effective approach to treat ovarian cancer and that WK369 has the potential to be used as a candidate therapeutic agent for ovarian cancer.